This invention relates to vaccines, vaccine compositions, methods of preparation of vaccines, and uses thereof in the prophylaxis and treatment of viral infections in mammalian patients (including humans). More specifically it relates to vaccines and vaccine compositions useful in combating a virus of the family Pox viridae, such as vaccinia virus (“VV”) and smallpox virus.
Vaccines against Pox viridae viruses, especially VV and small pox, are known, and have been used for many years with a large degree of success. However, adverse responses to standard doses of inocula is a problem quite frequently encountered in vaccination against VV and small pox. As a result, conventional vaccines cannot be administered to a significant fraction of the population who are either immune suppressed or who would otherwise react adversely to the establish vaccine protocols. This can amount to as many as 20% of the individuals targeted to be inoculated. More efficient inocula compositions, allowing smaller effective does, would be a significant advantage in this respect. Ineffectively vaccinated patients pose a severe threat of spread of the infectious disease
As vaccination against a variety of pathogens becomes more widespread, needs develop to increase the efficiency of the inocula, while reducing the sizes of the batches of vaccine required for vaccination of an entire population. This is particularly important during times of acute need (bio-terrorist attacks, emergent epidemic, for example) when rapid responses are required.
To increase vaccine potency and efficiency, a variety of adjuvants have been developed. These include Freund's complete adjuvant (FCA) which is an emulsion containing heat killed mycobacterium tuberculosis, which has proved to be too toxic for use in humans; cytokines such as IL-2 and IL-12, which elicit a Th-I response conducive to cytotoxic mechanisms in the immune system; and oil emulsion/aluminum salts containing immune stimulators (proinflammatory bacterial products). Many of these are too toxic for use in humans. Others cannot be implemented because their mode of action is obscure.
Preferred, effective vaccines and vaccine-adjuvant combinations should elicit both a humoral response and a cell mediated response in the mammalian subject. The humoral response causes the raising of antibodies specific to the antigens of the invading pathogen and results in lasting defense against future invasions of the same pathogen. The cell mediated response involves destruction of infected cells by killer T-cells, i.e. cytotoxic T-lymphocytes (“CTLs”).
It is known that the cytotoxic T-lymphocyte cell (CTL) response is a major component of the immune system, active in immune surveillance and destruction of infected cells and invading organisms expressing foreign antigen on their surface. A peptide fragment of the antigen binds to major histocompatiblity complex molecules (MHC) to form the ligand of the antigen specific T-cell receptor. Cytotoxic T-lymphocytes recognize peptide bound to MHC Class 1 molecules on the surface of the infected cells, and destroy them. For this to occur, a ternary complex must be formed in the cell and transported to the cell surface. The formation of the ternary complex is thought to involve the transport of peptides, generated by protein degradation in the cytoplasm of the cell, into the lumen of the endoplasmic reticulum (ER). This transport involves two genes located in the MHC region which encode proteins of the ATP binding cassette (ABC) family, call TAP-I and TAP-2 (Deverson, E. V. et al, “Nature” 348:738, 1990).